The Role of CPNE7 (Copine-7) in Colorectal Cancer Prognosis and Metastasis.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial-mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.

Upregulation of programmed death ligand-1 in tumor-associated macrophages affects chemotherapeutic response in ovarian cancer cells.

To better understand the mechanism of chemoresistance in ovarian cancer cells, we aimed to investigate the influence of macrophages on the tumor cell response to carboplatin and identify the genes associated with chemoresistance. We mimicked the tumor microenvironment (TME) using a co-culture technique and compared the proliferation of ovarian cells with and without macrophages. We also examined M1 and M2 marker expression and the expression of key TME genes. Post the co-culture, we treated ovarian cancer cells with carboplatin and elucidated the function of programmed death-ligand 1 (PD-L1) in carboplatin chemoresistance. We investigated CD68 and PD-L1 expression in normal and cancerous ovarian tissues using immunohistochemistry (IHC). Finally, we analyzed the association between CD68 or PD-L1 expression and survival outcomes. Inducible nitric oxide synthase (iNOS) was downregulated, while the gene expression of M2 macrophage markers was increased in ovarian cancer cells. PD-L1, vascular endothelial growth factor (VEGF), Interleukin (IL)-6, IL-10, IL-12, signal transducer and activator of transcription 3 (STAT3), B-cell lymphoma 2 (BCL2), multidrug resistance 1 (MDR1), and colony stimulating factor 1 (CSF-1) were upregulated. Notably, PD-L1 was upregulated in both the ovarian cancer cells and macrophages. Ovarian cancer cells co-cultured with macrophages exhibited statistically significant carboplatin resistance compared to single-cultured ovarian cancer cells. PD-L1 silencing induced chemosensitivity in both types of co-cultured ovarian cancer cells. However, IHC results revealed no correlation between PD-L1 expression and patient survival or cancer stage. CD68 expression was significantly increased in cancer cells compared to normal or benign ovarian tumor cells, but it was not associated with the survival outcomes of ovarian cancer patients. Our study demonstrated that ovarian cancer cells interact with macrophages to induce the M2 phenotype. We also established that PD-L1 upregulation in both ovarian cancer cells and macrophages is a key factor for carboplatin chemoresistance.

The Impact of Pre-Chemotherapy Body Composition and Immunonutritional Markers on Chemotherapy Adherence in Stage III Colorectal Cancer Patients.

Patients with colorectal cancer (CRC) often fail to complete full-course chemotherapy with a standard dose due to various reasons. This study aimed to determine whether body composition affects chemotherapy adherence in patients with CRC. The medical records of 107 patients with stage III CRC who underwent adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy at a single center between 2014 and 2018 were analyzed retrospectively. Blood test results for selected immunonutritional markers were analyzed and body composition was measured through computed tomography. Univariate and multivariate analyses were performed on low and high relative dose intensity (RDI) groups, based on an RDI of 0.85. In the univariate analysis, a higher skeletal muscle index was correlated with a higher RDI (p = 0.020). Psoas muscle index was also higher in patients with high RDI than in those with low RDI (p = 0.026). Fat indices were independent of RDI. Multivariate analysis was performed for the aforementioned factors and results showed that age (p = 0.028), white blood cell count (p = 0.024), and skeletal muscle index (p = 0.025) affected RDI. In patients with stage III CRC treated with adjuvant FOLFOX chemotherapy, a decrease in RDI was related to age, white blood cell count, and skeletal muscle index. Therefore, if we adjust the drug dosage in consideration of these factors, we can expect an increased treatment efficiency in patients by increasing chemotherapy compliance.

Intracellular delivery of oxaliplatin conjugate via cell penetrating peptide for the treatment of colorectal carcinoma in vitro and in vivo.

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC50. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.

Nanostructured mesophase electrode materials: modulating charge-storage behavior by thermal treatment.

3D nanostructured carbonaceous electrode materials with tunable capacitive phases were successfully developed using graphene/particulate polypyrrole (PPy) nanohybrid (GPNH) precursors without a separate process for incorporating heterogeneous species. The electrode material, namely carbonized GPNHs (CGPNHs) featured a mesophase capacitance consisting of both electric double-layer (EDL) capacitive and pseudocapacitive elements at the molecular level. The ratio of EDL capacitive element to pseudocapacitive element (E-to-P) in the mesophase electrode materials was controlled by varying the PPy-to-graphite weight (Pw/Gw) ratio and by heat treatment (TH), which was demonstrated by characterizing the CGPNHs with elemental analysis, cyclic voltammetry, and a charge/discharge test. The concept of the E-to-P ratio (EPR) index was first proposed to easily identify the capacitive characteristics of the mesophase electrode using a numerical algorithm, which was reasonably consistent with the experimental findings. Finally, the CGPNHs were integrated into symmetric two-electrode capacitor cells, which rendered excellent energy and power densities in both aqueous and ionic liquid electrolytes. It is anticipated that our approach could be widely extended to fabricating versatile hybrid electrode materials with estimation of their capacitive characteristics.

Graphene-Embedded Hydrogel Nanofibers for Detection and Removal of Aqueous-Phase Dyes.

A facile route to graphene/polymer hydrogel nanofibers was developed. An aqueous dispersion of graphene (containing >40% bilayer graphene flakes) stabilized by a functionalized water-soluble polymer with phenyl side chains was successfully electrospun to yield nanofibers. Subsequent vapor-phase cross-linking of the nanofibers produced graphene-embedded hydrogel nanofibers (GHNFs). Interestingly, the GHNFs showed chemical sensitivity to the cationic dyes methylene blue (MB) and crystal violet (CV) in the aqueous phase. The adsorption capacities were as high as 0.43 and 0.33 mmol g-1 s-1 for MB and CV, respectively, even in a 1.5 mL s-1 flow system. A density functional theory calculation revealed that aqueous-phase MB and CV dyes were oriented parallel to the graphene surface and that the graphene/dye ensembles were stabilized by secondary physical bonding mechanisms such as the π-π stacking interaction in an aqueous medium. The GHNFs exhibited electrochemical properties arising mainly from the electric double-layer capacitance, which were applied in a demonstration of GHNF-based membrane electrodes (5 cm in diameter) for detecting the dyes in the flow system. It is believed that the GHNF membrane can be a successful model candidate for commercialization of graphene due to its easy-to-fabricate process and remarkable properties.

Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors.

Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species.

The effect of nanoparticle packing on capacitive electrode performance.

Nanoparticles pack together to form macro-scale electrodes in various types of devices, and thus, optimization of the nanoparticle packing is a prerequisite for the realization of a desirable device performance. In this work, we provide in-depth insight into the effect of nanoparticle packing on the performance of nanoparticle-based electrodes by combining experimental and computational findings. As a model system, polypyrrole nanospheres of three different diameters were used to construct pseudocapacitive electrodes, and the performance of the electrodes was examined at various nanosphere diameter ratios and mixed weight fractions. Two numerical algorithms are proposed to simulate the random packing of the nanospheres on the electrode. The binary nanospheres exhibited diverse, complicated packing behaviors compared with the monophasic packing of each nanosphere species. The packing of the two nanosphere species with lower diameter ratios at an optimized composition could lead to more dense packing of the nanospheres, which in turn could contribute to better device performance. The dense packing of the nanospheres would provide more efficient transport pathways for ions because of the reduced inter-nanosphere pore size and enlarged surface area for charge storage. Ultimately, it is anticipated that our approach can be widely used to define the concept of "the best nanoparticle packing" for desirable device performance.